The long-term objective of the proposed project is to ascertain the role of spreading cortical depression (SCD) in migraine headache. Until now, the observation of spontaneous SCD has not been reported in humans, but a variety of phenomena, including the similarity of propagation speeds for SCD and scotomata of migraine, the marked dilatation of pial blood vessels accompanying SCD, and cerebral blood flow anomalies observed both in migraine with aura and SCD seem to imply a role for SCD in migraine. Recently, we have reported preliminary results of MEG (magnetoencephalographic) studies of SCD in rabbit and rat models and very similar signals in human subjects with migraine strongly suggest that SCD may indeed be present in migraine, both during headache and occasionally interictally. A more recent blinded study of migraine patients and normals tended to confirm the former results. In the proposed study, a number of migraine patients, patient with non-migrainous headache, and normal controls will be studied using MEG, and SCD will be studied in animals with gyrencephalic cortex. Specific aims include: 1) To confirm the findings of pilot data which have shown characteristic neuromagnetic signals in migraine subjects but not controls, 2) to compare neuromagnetic signals at various stages of migraine attack with chronic tension-type headache, and 3) to expand MEG studies to gyrencephalic species in order to more accurately compare with MEG signals obtained from human studies of migraine. Satisfying these aims involves a systematic study of migraine with aura and migraine without aura and non-migrainous headache throughout the headache and during postictal and interictal phases as well as normal controls, and ferret and pig models of SCD. All subjects will be monitored in the same manner for at least 30 minutes with the MEG probe at several positions. Simultaneous EEG and EOG will be used to monitor the state of arousal of the patient. Data analysis will consist of a systematic search for DC field shifts associated with SCD, large amplitude biphasic magnetic waves presumed to arise when SCD follows a sulcus, and for suppression of spontaneous brain activity not associated with change in arousal, findings which were observed in preliminary studies. A variety of techniques, some currently under development, will be used to detect artifactual signals arising from both the patient and the environment, and to distinguish SCD signals from other naturally occurring ones, such as changes in the subject's state of arousal. The projected result will be a statistically significant evaluation for the presence or absence of signals associated with SCD in migraine patients and controls. Animal studies will employ a KC1 model of SCD in ferrets and pigs. Signal obtained during SCD will be compared qualitatively and quantitatively with those obtained from migraine subjects.